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Bile acids exhibit strong antimicrobial activity as natural detergents, and are involved in lipid digestion and absorption. We investigated the mechanism of bile acid adaptation in Lactobacillus gasseri JCM1131T. Exposure to sublethal concentrations of cholic acid (CA), a major bile acid in humans, resulted in development of resistance to otherwise-lethal concentrations of CA by this intestinal lactic acid bacterium. As this adaptation was accompanied by decreased cell-membrane damage, we analyzed the membrane lipid composition of L. gasseri. Although there was no difference in the proportions of glycolipids (~70%) and phospholipids (~20%), adaptation resulted in an increased abundance of long-sugar-chain glycolipids and a 100% increase in cardiolipin (CL) content (to ~50% of phospholipids) at the expense of phosphatidylglycerol (PG). In model vesicles, the resistance of PG vesicles to solubilization by CA increased with increasing CL/PG ratio. Deletion of the two putative CL synthase genes, the products of which are responsible for CL synthesis from PG, decreased the CL content of the mutants, but did not affect their ability to adapt to CA. Exposure to CA restored the CL content of the two single-deletion mutants, likely due to the activities of the remaining CL synthase. In contrast, the CL content of the double-deletion mutant was not restored, and the lipid composition was modified such that PG predominated (~45% of total lipids) at the expense of glycolipids. Therefore, CL plays important roles in bile acid resistance and maintenance of the membrane lipid composition in L. gasseri.

Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability. Preclinical studies show that the systemic administration of umbilical cord blood cells (UCBCs) is beneficial for neonatal HIE. We conducted a single-arm clinical study to examine the feasibility and safety of intravenous infusion of autologous UCBCs for newborns with HIE. When a neonate was born with severe asphyxia, the UCB was collected, volume-reduced, and divided into three doses. The processed UCB was infused at 12–24, 36–48, and 60–72 hours after the birth. The designed enrolment was six newborns. All six newborns received UCBC therapy strictly adhering to the study protocol together with therapeutic hypothermia. The physiological parameters and peripheral blood parameters did not change much between pre- and postinfusion. There were no serious adverse events that might be related to cell therapy. At 30 days of age, the six infants survived without circulatory or respiratory support. At 18 months of age, neurofunctional development was normal without any impairment in four infants and delayed with cerebral palsy in two infants. This pilot study shows that autologous UCBC therapy is feasible and safe.

Background: Serum creatinine (SCr) is widely used to test renal function. SCr at birth is strongly affected by maternal SCr and does not reflect the renal function of the neonate. Serum cystatin C (CysC) has been used as an indicator of glomerular filtration rate in adults and children. However, CysC has not been widely used to evaluate kidney function in neonates until now. Methods: The renal function of neonates admitted to our neonatal intensive care unit was evaluated by analyzing cord blood CysC levels at birth using a latex immunoturbidimetric assay. Results: The cord blood CysC and SCr of ten neonates was measured at birth. The CysC levels of four patients without impaired renal function were between 1.26 and 1.53 mg/L. The CysC level in one case whose mother was diagnosed with chronic kidney disease was not elevated (1.60 mg/L), although the patient’s SCr level was elevated (2.25 mg/dL). The CysC levels of three patients with acute kidney injury due to asphyxia were slightly higher (1.78 to 2.17 mg/L) than those in patients without acute kidney disease. The CysC levels of two patients diagnosed with renal failure were substantially higher (4.09 and 7.07 mg/L) than those of patients without renal failure. Conclusion: CysC shows potential as a useful marker to evaluate the kidney function of neonates at birth, as CysC is not affected by maternal CysC.

Umbilical cord blood (UCB) cells could be a useful adjunct intervention for infants with HIE. We report our clinical experience of UCB stem cell transplantation in infants with HIE. We selected patients for UCB stem cell transplantation based on following criteria; (1) moderate or severe HIE according to the classification of Sarnat II or III and Thompson score ≥10 points, (2) gestational age ≥36 weeks, (3) body weight at birth >1800 g, (4) born by cesarean section under general anesthesia, and (5) inborn baby. Cases in which collected UCB volume is below 40 mL were excluded from this trial. Brain hypothermia therapy (BHT) was performed simultaneously under supportive mechanical ventilation with sedative agents (fentanyl citrate and midazolam). After collected UCB, CD34-positive cells were separated by SEPAX-2™ (Biosafe SA, Eysins/Nyon, Switzerland) and were transfused to the babies once a day for 12 h to 3 days.

腎盂腎炎の再発予防内服と早期の放射線画像診断の妥当性に関して，当施設で米国小児科学会のPractice Parameterに準じて長期管理を行った164例 (男児121例，女児43例) について後方視的に検討した。初回の腎盂腎炎のあとに排尿時膀胱尿道造影検査を行った。膀胱尿管逆流 (VUR) を認めず予防内服を行わなかった32例のうち9例 (28%) が再発したのに対し，予防内服を行った症例の再発はVUR I～III度15例中2例 (13%)，IV・V度10例中5例 (50%) であった。DMSAシンチのVUR検出率はIII～V度の症例でも73% (11例中8例) にとどまった。発熱から24時間以内に治療開始された15例のうち6例に放射性同位体の取り込み欠損を認めた。1歳未満ではIII～V度のVURでも11例中7例が改善していた。これらの検討より，現時点では管理手順を変える必然性は見いだせなかった。

小児特発性ネフローゼ症候群において免疫抑制剤シクロフォスファミド (CPM) を使用した43例についてその有効性を検討した。CPMはステロイド依存性・頻回再発型ネフローゼ症候群に対して免疫抑制剤の第一選択として使用し，2mg/kg/dayを8～12週間投与した。平均観察期間108.4ヵ月 (25～330ヵ月) における寛解維持率は，6ヵ月65%，12ヵ月53%，24ヵ月39%，36ヵ月32%，48ヵ月30%であった。CPM有効の定義を，頻回再発型ネフローゼ症候群;CPM投与後，6ヵ月間再発がなかった例，ステロイド依存性ネフローゼ症候群;CPM投与前後での再発時のPSL量が1/2以下に減少した例として検討した。CPM有効例は29例 (67%)，無効例は14例 (33%) であった。また，CPM使用後にそれ以外の免疫抑制剤を使用した例では，CPM有効例は無効例に比し，CPM以外の免疫抑制剤使用までの期間が平均32ヵ月間長い傾向にあった。

Introduction: The standard dose of intravenous immunoglobulin (IVIG) as initial therapy for patients with Kawasaki disease (KD) is generally 2 g/kg. In our hospital, the initial IVIG dose for patients with KD is 1 g/kg, which is augmented according to treatment response, and therapy is changed to plasma exchange (PE) if IVIG therapy over 6 g/kg is ineffective. To date, various factors and scoring systems for predicting IVIG resistance have been reported. We evaluated consecutive urinary β2 microglobulin to creatinine ratio (β2MG/Cr) data as a possible predictive factor of IVIG therapy resistance. Objectives: To clarify whether urinary β2MG/Cr is an effective predictive factor for IVIG therapy resistance. Methods: We retrospectively reviewed the data of all patients with KD who underwent IVIG therapy at a dose of over 6g/kg in our hospital from January 1997 to January 2014. Patients with recurrent KD were excluded from the study. Patients were divided into two groups for analysis, those who did and did not require PE. Factors including urinary β2MG/Cr were compared across the two groups. We used the peak urinary β2MG/Cr of each patient in the course of the disease. Results: There were 713 patients with KD who were treated in our hospital from January 1997 to January 2014. There were 28 patients without recurrent KD who underwent IVIG therapy over 6g/kg. IVIG was successful in 24 patients (non-PE group), and 4 patients required PE (PE group). Urinary β2MG/Cr was not measured in only one patient of the non-PE group. Urinary β2MG/Cr significantly higher in the PE group (median 119,228 μg/gCr, 69,286-234,290 μg/gCr) compared to the non-PE group (median 12,270 μg/gCr, 1,981-210,647 μg/gCr) (p=0.001, t-test). Urinary β2MG/Cr exceeded 100,000 μg/gCr in 4 % (1 of 23) of the PE group and 75 % (3 of 4) of non-PE group. There were temporarily coronary artery lesions (dilation or aneurysm) in 57 % (13 of 23) of the non-PE group and 75 % (3 of 4) of the PE group. Coronary artery lesions regressed in all patients. Conclusion: Our study suggests that urinary β2MG/Cr measurement is a useful non-invasive test for predicting IVIG resistance.

A series of biodegradable polyesters, poly[(R)-3-hydroxybutyrate] (PHB), poly(-caprolactone) (PCL), and polyglycolide (PGA), were found to be effective crystallization-accelerating agents for poly(l-lactide) (PLLA). Differential scanning calorimetry and polarized optical microscopy strongly suggested that the accelerated crystallization of PLLA in the presence of the three biodegradable polyesters is attributable to a nucleation-assisting effect of PCL and PGA and a spherulite growth-accelerating effect of PHB, although the incorporated PHB lowered the spherulite number of PLLA per unit area. The spherulite growth-accelerating effect of PHB probably resulted from the relatively high miscibility of PLLA with PHB and the low glass transition temperature of PHB compared to that of PLLA. The crystallization kinetics of PLLA varied only in the case of PLLA/PHB blends during cooling from the melt, as evidenced by the nucleation constant and radius growth rate values of the spherulites. The nucleation and growth types of PLLA crystallites are thought to be altered only in the case of PLLA/PGA blends during heating, as evidenced by Avrami exponent n values.

The low-temperature physical aging of amorphous poly(L-lactide) (PLLA) at 25–50°C below glass transition temperature (Tg) was carried out for 90 days. The physical aging significantly increased the Tg and glass transition enthalpy, but did not cause crystallization, regardless of aging temperature. The nonisothermal crystallization of PLLA during heating was accelerated only by physical aging at 50°C. These results indicate that the structure formed by physical aging only at 50°C induced the accelerated crystallization of PLLA during heating, whereas the structure formed by physical aging at 25 and 37°C had a negligible effect on the crystallization of PLLA during heating, except when the physical aging at 37°C was continued for the period as long as 90 days. The mechanism for the accelerated crystallization of PLLA by physical aging is discussed. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010